Japanese researchers engineered next-generation CAR-T therapies exploiting Eva1 (MPZL2) protein expressed on lung, pancreatic, and liver cancers. This antigen’s small size enables stronger immunological synapse formation, enhancing T-cell activation and tumor killing efficacy. The study highlights engineered spacer and intracellular domains optimizing CAR-T cell persistence and cytotoxicity against solid tumor microenvironments, potentially overcoming limitations of current hematological-focused immunotherapies.